pH/redox dual-sensitive platinum (IV)-based micelles with greatly enhanced antitumor effect for combination chemotherapy.

Abstract

To achieve precise control of nano-carrier structure and drug release behavior, we designed a pH/redox dual-responsive polymeric prodrug by condensation polymerization using octahedrally coordinated cisplatin (Pt IV) and ortho ester monomer. The prodrug was then self-assembled with doxorubicin (DOX) in aqueous solution to give a synergetic drug delivery system. The polymer backbone can completely degrade and release cisplatin (Pt II) and DOX under the acidic and reductive environment of tumor cells, owing to the breakage of ortho ester bonds and the reduction of Pt (IV). The size and micromorphology of micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro study of drug release, cellular uptake and cytotoxicity revealed that the micelles could be triggered intracellularly to release two drugs. In vivo drug distribution and antitumor activity also provide the evidence for the excellent antitumor effect of micelles.

• Authors: Le He, Min Sun, Xu Cheng, Yong Xu, Xiaodong Lv, Xin Wang, Rupei Tang
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 541 Pg. 30-41 (Apr 01 2019) ISSN: 1095-7103 [Electronic] United States
• PMID: 30682591 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Drug Carriers
• Micelles
• Doxorubicin
• Cisplatin

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Cisplatin (administration & dosage, chemistry)
• Doxorubicin (administration & dosage)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Humans
• Hydrogen-Ion Concentration
• Liver Neoplasms (drug therapy, pathology)
• Micelles
• Oxidation-Reduction
• Tumor Cells, Cultured